Darren Linkin, M.D. is a post-doctoral research fellow in Infectious Diseases at the University of Pennsylvania and a student in the Masters of Science in Clinical Epidemiology in the Center for Clinical Epidemiology and Biostatistics (CCEB). Emerging infections and antimicrobial drug use are his main research focus; an integrated five-year educational and research program is proposed to facilitate his growth as a successful independent clinical investigator in the field. The training plan includes outstanding mentorship from an international expert in pharmacoepidemiology and input from a diverse team of experienced clinical investigators. Advanced coursework will be performed in epidemiology, quasi-experimental studies, clinical trials, and pharmacoepidemiology. Hospital-acquired pneumonia (HAP) is a common disease that confers high mortality, yet it is relatively poorly understood. Only recently have any studies attempted to determine how superinfections additional infections arising during treatment for HAP--contribute to its mortality. Superinfection has been associated with a two-fold increase in mortality of HAP. Death in a significant proportion of HAP patients may also be due to subsequent extra-pulmonary infections. The specific aims of this proposal are to: 1) describe the epidemiology of clinical superinfection in intensive care unit (ICU) patients treated for HAP, 2) determine risk factors for clinical superinfection in HAP patients in the ICU, and 3) determine the impact of superinfection on in-hospital mortality in these patients. ICU patients with HAP will be enrolled into a prospective cohort. Exposures to be examined include duration and spectra of antibiotic use, and severity of illness as measured by Apache II score. Superinfection and extra-pulmonary infection will be defined by both clinical and microbiological criteria. A Cox proportional hazards model will be used to determine independent risk factors for superinfection, as well as the effect of superinfection and other factors on death. The proposed study will further our understanding of the biology of superinfection, add to clinical knowledge guiding the treatment of HAP, and lay the groundwork for future interventional studies to improve outcomes in HAP patients and other patients at risk for infectious complications of antimicrobial therapy.